"Multidisciplinary fast-track" care can significantly reduce risk of mortality among hip fracture patients at least 80 years old: a single-center retrospective study.

BACKGROUND: "Multidisciplinary fast-track" (MFT) care can accelerate recovery and improve prognosis after surgery, but whether it is effective in older people after hip fracture surgery is unclear. METHODS: We retrospectively compared one-year all-cause mortality between hip fracture patients at least 80 years old at our institution who underwent hip fracture surgery between January 2014 and December 2018 and who then received MFT or conventional care. Multivariable regression was used to assess the association between MFT care and mortality after adjustment for confounders. RESULTS: The final analysis included 247 patients who received MFT care and 438 who received conventional orthopedic care. The MFT group showed significantly lower one-year mortality (8.9% vs. 14.4%, P = 0.037). Log-rank testing of Kaplan-Meier survival curves confirmed the survival advantage. However, the two groups did not differ significantly in rates of mortality during hospitalization or at 30 or 90 days after surgery. Regression analysis confirmed that MFT care was associated with lower risk of one-year mortality (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.281-0.788, P = 0.04), and the survival benefit was confirmed in subgroups of patients with anemia (HR 0.453, 95% CI 0.268-0.767, P = 0.003) and patients with American Society of Anesthesiologists grade III (HR 0.202, 95% CI 0.08-0.51, P = 0.001). CONCLUSIONS: MFT care can reduce one-year mortality among hip fracture patients at least 80 years old. This finding should be verified and extended in multi-center randomized controlled trials.

SHH induces macrophage oxidative phosphorylation and efferocytosis to promote scar formation.

Excessive scar formation such as hypertrophic scars and keloids, resulting from trauma or surgical procedures, present a widespread concern for causing disfigurement, discomfort, and functional limitations. Macrophages play pivotal roles in maintaining tissue homeostasis, orchestrating tissue development, repair, and immune responses, and its transition of function and phenotype plays a critical role in regulating the balance between inflammation and tissue regeneration, which is central to cutaneous scar formation. Recent evidence suggests the involvement of Sonic Hedgehog (SHH) in the induction of anti-inflammatory M2-like macrophage phenotypes within tumor microenvironments. In our study, we observed increased SHH expression in human hypertrophic scars, prompting an investigation into its influence on macrophage polarization, efferocytosis, and cutaneous scar formation. Our findings reveal that SHH can enhance oxidative phosphorylation (OXPHOS) in macrophages, augment macrophage efferocytosis, and promote M2 polarization, finally contributing to the progression of cutaneous scar formation. Notably, targeting SHH signaling with vismodegib exhibited promising potential in mitigating scar formation by reversing the effects of enhanced OXPHOS and M2 polarization in macrophages. In conclusion, this study underscores the critical roles of macrophage metabolism, particularly OXPHOS, efferocytosis and SHH signaling in cutaneous scar formation. Understanding these mechanisms provides new avenues for potential interventions and scar prevention strategies.

Chronic Postsurgical Pain Following Lung Transplantation: Characteristics, Risk Factors, Treatment, and Prevention: A Narrative Review.

Chronic pain after lung transplantation (LTx) can substantially reduce quality of life (QoL), yet current consensus guidelines say little about how to prevent or manage it. Research on pain after LTx has tended to focus on acute rather than chronic pain, and it has not extensively examined the factors associated with onset or resolution of chronic pain, which differ from factors influencing chronic pain after general thoracic surgery. This narrative review explores what is known about the epidemiology and risk factors of chronic pain after LTx, as well as effective ways to treat or prevent it. The review identifies key questions and issues that should be the focus of future research.

Predictive modeling for identifying infection risk following spinal surgery: Optimizing patient management.

Infection is known to occur in a substantial proportion of patients following spinal surgery and predictive modeling may provide a useful means for identifying those at higher risk of complications and poor prognosis, which could help optimize pre- and postoperative management strategies. The outcome measure of the present study was to investigate the occurrence of all-cause infection during hospitalization following scoliosis surgery. To meet this aim, the present study retrospectively analyzed 370 patients who underwent surgery at the Second Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China) between January 2016 and October 2022, and patients who either experienced or did not experience all-cause infection while in hospital were compared in terms of their clinicodemographic characteristics, surgical variables and laboratory test results. Logistic regression was subsequently applied to data from a subset of patients in order to build a model to predict infection, which was validated using another subset of patients. All-cause, in-hospital postoperative infections were found to have occurred in 66/370 patients (17.8%). The following variables were included in a predictive model: Sex, American Society of Anesthesiologists (ASA) classification, body mass index (BMI), diabetes mellitus, hypertension, preoperative levels of white blood cells and preoperative C-reactive protein (CRP) and duration of surgery. The model exhibited an area under the curve of 0.776 against the internal validation set. In conclusion, dynamic nomograms based on sex, ASA classification, BMI, diabetes mellitus, hypertension, preoperative levels of white blood cells and CRP and duration of surgery may have the potential to be a clinically useful predictor of all-cause infection following scoliosis. The predictive model constructed in the present study may potentially facilitate the real-time visualization of risk factors associated with all-cause infection following surgical procedures.

Magnolin alleviated DSS-induced colitis by inhibiting ALOX5-mediated ferroptosis.

Inflammatory bowel disease (IBD) is a chronic and incurable disorder associated with higher cancer risk and currently faces unsatisfactory treatment outcomes. Ferroptotic cells secrete damage-associated molecular patterns (DAMPs) that recruit and activate immune cells, particularly macrophages. Magnolin has excellent antioxidant and anti-inflammatory properties, but its effect on IBD has not yet been clearly understood. This study aimed to investigate the therapeutic effects and mechanism of magnolin in IBD. For this purpose, in vivo and in vitro colitis models were established using dextran sulfate sodium (DSS), followed by optimization of magnolin concentration 2.5 µg/mL in vitro and 5 mg/kg in vivo. Bioinformatics analysis identified potential magnolin target sites and evaluated ferroptosis-associated gene expressions. Body weight, food intake, disease activity index (DAI), pathological changes, and inflammation levels were assessed. The effect of magnolin on ferroptosis and macrophages was evaluated using quantitative real time-polymerase chain reaction (qRT-PCR), immunofluorescent staining, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and western blotting. Results indicated that magnolin at a lower dose (5 mg/kg) alleviated DSS-induced colitis symptoms and reduced inflammation in mice. The bioinformatics analysis showed arachidonate 5-lipoxygenase (ALOX5) as a potential magnolin target. Furthermore, magnolin inhibited the expression of ALOX5 with no effect on GPX4. Moreover, magnolin regulated macrophage differentiation into the M2 phenotype and suppressed pro-inflammatory factors, that is, interleukin-6 and tumor necrosis factor-α (IL-6 and TNFα). These results suggested that magnolin possesses significant therapeutic potential in treating IBD by suppressing ALOX5-mediated ferroptosis, inhibiting M1 while promoting M2 macrophages, which is envisaged to provide novel strategies for treating IBD.

Nomogram for predicting postoperative pulmonary complications in spinal tumor patients.

OBJECTIVES: Although several independent risk factors for postoperative pulmonary complications (PPCs) after spinal tumor surgery have been studied, a simple and valid predictive model for PPC occurrence after spinal tumor surgery has not been developed. PATIENTS AND METHODS: We collected data from patients who underwent elective spine surgery for a spinal tumor between 2013 and 2020 at a tertiary hospital in China. Data on patient characteristics, comorbidities, preoperative examinations, intraoperative variables, and clinical outcomes were collected. We used univariable and multivariable logistic regression models to assess predictors of PPCs and developed and validated a nomogram for PPCs. We evaluated the performance of the nomogram using the area under the receiver operating characteristic curve (ROC), calibration curves, the Brier Score, and the Hosmer-Lemeshow (H-L) goodness-of-fit test. For clinical use, decision curve analysis (DCA) was conducted to identify the model's performance as a tool for supporting decision-making. RESULTS: Among the participants, 61 (12.4%) individuals developed PPCs. Clinically significant variables associated with PPCs after spinal tumor surgery included BMI, tumor location, blood transfusion, and the amount of blood lost. The nomogram incorporating these factors showed a concordance index (C-index) of 0.755 (95% CI: 0.688-0.822). On internal validation, bootstrapping with 1000 resamples yielded a bias-corrected area under the receiver operating characteristic curve of 0.733, indicating the satisfactory performance of the nomogram in predicting PPCs. The calibration curve demonstrated accurate predictions of observed values. The decision curve analysis (DCA) indicated a positive net benefit for the nomogram across most predicted threshold probabilities. CONCLUSIONS: We have developed a new nomogram for predicting PPCs in patients who undergo spinal tumor surgery.

SERS-Temperature Dual-Mode T-type Lateral Flow Strip for Accurate Detection of Free and Total Prostate-Specific Antigens in Blood.

Accurate point-of-care (POC) analysis of cancer markers is the essence in the comprehensive early screening and treatment of cancer. Dual-mode synchronous detection is one of the effective approaches to reduce the probability of false negatives or false positives. As a result, this can greatly improve the accuracy of diagnosis. In this work, a surface-enhanced Raman scattering (SERS)-temperature dual-mode T-type lateral flow strip was fabricated to direct and simultaneous POC detection of total and free prostate-specific antigens (t-PSA and f-PSA) in blood. With the advantage of high stability of T-type lateral flow strip and simultaneous acquirement of assay results for t-PSA and f:t PSA ratio, the proposed method has high accuracy in the diagnosis of prostate cancer, especially in the diagnostic gray zone between 4.0 and 10.0 ng/mL. The SERS-temperature dual-signal has a good linear correlation with either f-PSA or t-PSA. To evaluate the clinical diagnostic performance of the proposed method, spiked human serum samples and the whole blood sample were analyzed. The assay results showed good recovery, and compared with traditional electrochemiluminescence immunoassay (ECLIA) method (t-PSA: 43.151; f/t ratio: 0.08), the results obtained by the proposed method were similar (t-PSA: 40.15 (SERS), 36.21 (temperature); f/t ratio: 0.08 (SERS), 0.08 (temperature), but the detection time (15 min) and cost ($0.05) had been greatly reduced. Therefore, the proposed SERS-temperature synchronous dual-mode T-type lateral flow strip has a strong application potential in the field of accurate large-scale diagnostics of prostate cancer on-site by simultaneous POC detection of t-PSA and f-PSA in blood.

The evaluation of four nano-formulations loaded-Elsinochrome A on characteristics and in vitro cytotoxicity effect.

Elsinochrome A (EA) is a naturally occurring photosensitizer with potential applications in photodynamic therapy (PDT) for various malignancies. Despite its promising therapeutic properties, the poor solubility of EA hampers its effective utilization in clinical settings. To circumvent this limitation, we engineered four distinct nano-formulations: PLGA/EA nanoparticles (NPs), CMC-PLGA/EA NPs, mPEG-PCL/EA nanomicelles (NMs), and LHP-CHOL/EA nanoliposomes (NLs), all designed to enhance the solubility of EA. A comparative evaluation of these formulations, based on metrics such as particle size, Zeta potential, drug loading efficiency, and encapsulation efficiency, identified PLGA/EA NPs and mPEG-PCL/EA NMs as the most efficacious candidates. Subsequent in vitro investigations into the drug release kinetics under varying pH conditions and the impact on cell viability and apoptosis in A549 and MCF-7 cell lines were conducted. Remarkably, the maximum drug release for PLGA/EA NPs and mPEG-PCL/EA NMs was recorded at 62.5% and 70.8% in an acidic environment (pH 5.7), respectively. Upon exposure to 460 nm light, PLGA/EA NPs induced a significant reduction in A549 cell viability to 13.8% and an apoptosis rate of 93.8%, whereas mPEG-PCL/EA NMs elicited a decrease in MCF-7 cell viability to 12.8% and an apoptosis rate of 73.0%.

Risk Factors for Hypocoagulability After Cardiac Surgery: A Retrospective Study.

Hemostatic disturbances after cardiac surgery can lead to excessive postoperative bleeding. Thromboelastography (TEG) was employed to evaluate perioperative coagulative alterations in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), investigating the correlation between factors concomitant with cardiac surgery and modifications in coagulation. Coagulation index as determined by TEG correlated significantly with postoperative bleeding at 24-72 h after cardiac surgery (P < .001). Among patients with a normal preoperative coagulation index, those with postoperative hypocoagulability showed significantly lower nadir temperature (P = .003), larger infused fluid volume (P = .003), and longer CPB duration (P = .033) than those with normal coagulation index. Multivariate logistic regression showed that nadir intraoperative temperature was an independent predictor of postoperative hypocoagulability (adjusted OR: 0.772, 95% CI: 0.624-0.954, P = .017). Multivariate linear regression demonstrated linear associations of nadir intraoperative temperature (P = .017) and infused fluid volume (P = .005) with change in coagulation index as a result of cardiac surgery. Patients are susceptible to hypocoagulability after cardiac surgery, which can lead to increased postoperative bleeding. Ensuring appropriate temperature and fluid volume during cardiac surgery involving CPB may reduce risk of postoperative hypocoagulability and bleeding.

Nadir Hemoglobin Concentration After Spinal Tumor Surgery: Association With Risk of Composite Adverse Events.

STUDY DESIGN: Retrospective case-control study. OBJECTIVE: To explore the association of early postoperative nadir hemoglobin with risk of a composite outcome of anemia-related and other adverse events. METHODS: We retrospectively analyzed data from spinal tumor patients who received intraoperative blood transfusion between September 1, 2013 and December 31, 2020. Uni- and multivariate logistic regression was used to explore relationships of clinicodemographic and surgical factors with risk of composite in-hospital adverse events, including death. Subgroup analysis explored the relationship between early postoperative nadir hemoglobin and composite adverse events. RESULTS: Among the 345 patients, 331 (95.9%) experienced early postoperative anemia and 69 (20%) experienced postoperative composite adverse events. Multivariate logistic regression analysis showed that postoperative nadir Hb (OR = .818, 95% CI: .672-.995, P = .044), ASA ≥3 (OR = 2.007, 95% CI: 1.086-3.707, P = .026), intraoperative RBC infusion volume (OR = 1.133, 95% CI: 1.009-1.272, P = .035), abnormal hypertension (OR = 2.199, 95% CI: 1.085-4.457, P = .029) were correlated with composite adverse events. The lumbar spinal tumor was associated with composite adverse events with a decreased odds compared to thoracic spinal tumors (OR = .444, 95% CI: .226-.876, P = .019). Compared to patients with postoperative nadir hemoglobin ≥11.0 g/dL, those with nadir <9.0 g/dL were at significantly higher risk of postoperative composite adverse events (OR = 2.709, 95% CI: 1.087-6.754, P = .032). CONCLUSION: Nadir hemoglobin <9.0 g/dL after spinal tumor surgery is associated with greater risk of postoperative composite adverse events in patients who receive intraoperative blood transfusion.

Synthesis of lipoic acid ferulate and evaluation of its ability to preserve fish oil from oxidation during accelerated storage.

Lipoic acid ferulate (LAF) was synthesized and its anti-free radical ability in vitro was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonicacid) (ABTS) assays. Protective effects of LAF in stabilizing fish oil were tested, compared to antioxidants such as lipoic acid, ferulic acid and tert-butylhydroxyquinone (TBHQ) by measuring peroxide values, thiobarbituric acid reactants, p-anisidine values, nuclear magnetic resonance (NMR) spectra and gas chromatography-mass spectrometry (GC-MS) spectra of fish oil during accelerated storage (12 days, 80 °C). The inhibitory effect of these antioxidants on fish oil oxidation followed the order TBHQ ≧ LAF > ferulic acid > lipoic acid. In addition, the omega-3 polyunsaturated fatty acids were the first to be oxidized. The formation of oxidation products followed a first-order kinetic model, and the addition of LAF effectively reduced the reaction rate constants. Therefore, LAF can effectively slow down the formation of oxidative products and prolong the shelf life of fish oil.

Elsinochrome A induces cell apoptosis and autophagy in photodynamic therapy.

Elsinochrome A (EA) is a perylene quinone natural photosensitizer, photosensitizer under light excitation generates reactive oxygen species (ROS) to induce apoptosis, so can be used for treating tumors, that is so-called photodynamic therapy (PDT). However, the molecular mechanism, especially related to apoptosis and autophagy, is still unclear. In this study, we aimed to explore the mechanism of EA-PDT-induced B16 cells apoptosis and autophagy. The action of EA-PDT on mitochondrial permeability transition pore (MPTP), mitochondrial membrane potential (MMP) and the mitochondrial function were researched by fluorescence technique and Extracellular Flux Analyzer. Illumina sequencing, tandem mass tags Quantitative Proteomics and Western Blot studied the mechanism at the gene and protein levels. The results indicated that EA-PDT had excellent phototoxicity in vitro. EA could bind to the mitochondria. EA-PDT for 5 min caused MPTP opening, MMP decreasing and abnormal mitochondrial function with a concentration-dependent characteristic. EA-PDT resulted in an increase intracellular ROS and the number of autophagosomes. Caspase2, caspase9 and tnf were upregulated, and bcl2, prkn, atg2, atg9 and atg10 were downregulated. Our results indicated that EA-PDT induced cell apoptosis and autophagy through the mediation of ROS/Atg/Parkin. This study can provide enlightenment for exploring potential targets of drug development for the PDT of melanoma.

Microglia sense and suppress epileptic neuronal hyperexcitability.

Microglia are the resident immune cells of the central nervous system, undertaking surveillance role and reacting to brain homeostasis and neurological diseases. Recent studies indicate that microglia modulate epilepsy-induced neuronal activities, however, the mechanisms underlying microglia-neuron communication in epilepsy are still unclear. Here we report that epileptic neuronal hyperexcitability activates microglia and drives microglial ATP/ADP hydrolyzing ectoenzyme CD39 (encoded by Entpd1) expression via recruiting the cAMP responsive element binding protein (CREB)-regulated transcription coactivator-1 (CRTC1) from cytoplasm to the nucleus and binding to CREB. Activated microglia in turn suppress epileptic neuronal hyperexcitability in a CD39 dependent manner. Disrupting microglial CREB/CRTC1 signaling, however, decreases CD39 expression and diminishes the inhibitory effect of microglia on epileptic neuronal hyperexcitability. Overall, our findings reveal CD39-dependent control of epileptic neuronal hyperexcitability by microglia is through an excitation-transcription coupling mechanism.

Causal relationship between obesity and iron deficiency anemia: a two-sample Mendelian randomization study.

Background: Observational studies have suggested an association between obesity and iron deficiency anemia, but such studies are susceptible to reverse causation and residual confounding. Here we used Mendelian randomization to assess whether the association might be causal. Methods: Data on single-nucleotide polymorphisms that might be associated with various anthropometric indicators of obesity were extracted as instrumental variables from genome-wide association studies in the UK Biobank. Data on genetic variants in iron deficiency anemia were extracted from a genome-wide association study dataset within the Biobank. Heterogeneity in the data was assessed using inverse variance-weighted regression, Mendelian randomization Egger regression, and Cochran's Q statistic. Potential causality was assessed using inverse variance-weighted, Mendelian randomization Egger, weighted median, maximum likelihood and penalized weighted median methods. Outlier SNPs were identified using Mendelian randomization PRESSO analysis and "leave-one-out" analysis. Results: Inverse variance-weighted regression associated iron deficiency anemia with body mass index, waist circumference, trunk fat mass, body fat mass, trunk fat percentage, and body fat percentage (all odds ratios 1.003-1.004, P ≤ 0.001). Heterogeneity was minimal and no evidence of horizontal pleiotropy was found. Conclusion: Our Mendelian randomization analysis suggests that obesity can cause iron deficiency anemia.

Martynoside rescues 5-fluorouracil-impaired ribosome biogenesis by stabilizing RPL27A.

Martynoside (MAR), a bioactive component in several well-known tonic traditional Chinese herbs, exhibits pro-hematopoietic activity during 5-fluorouracil (5-FU) treatment. However, the molecular target and the mechanism of MAR are poorly understood. Here, by adopting the mRNA display with a library of even-distribution (md-LED) method, we systematically examined MAR-protein interactions in vitro and identified the ribosomal protein L27a (RPL27A) as a key cellular target of MAR. Structural and mutational analysis confirmed the specific interaction between MAR and the exon 4,5-encoded region of RPL27A. MAR attenuated 5-FU-induced cytotoxicity in bone marrow nucleated cells, increased RPL27A protein stability, and reduced the ubiquitination of RPL27A at lys92 (K92) and lys94 (K94). Disruption of MAR binding at key residues of RPL27A completely abolished the MAR-induced stabilization. Furthermore, by integrating label-free quantitative ubiquitination proteomics, transcriptomics, and ribosome function assays, we revealed that MAR restored RPL27A protein levels and thus rescued ribosome biogenesis impaired by 5-FU. Specifically, MAR increased mature ribosomal RNA (rRNA) abundance, prevented ribosomal protein degradation, facilitated ribosome assembly, and maintained nucleolar integrity. Collectively, our findings characterize the target of a component of Chinese medicine, reveal the importance of ribosome biogenesis in hematopoiesis, and open up a new direction for improving hematopoiesis by targeting RPL27A.

A novel model for predicting a composite outcome of major complications after valve surgery.

Background: On-pump valve surgeries are associated with high morbidity and mortality. The present study aimed to reliably predict a composite outcome of postoperative complications using a minimum of easily accessible clinical parameters. Methods: A total of 7,441 patients who underwent valve surgery were retrospectively analyzed. Data for 6,220 patients at West China Hospital of Sichuan University were used to develop a predictive model, which was validated using data from 1,221 patients at the Second Affiliated Hospital of Zhejiang University School of Medicine. The primary outcome was a composite of major complications: all-cause death in hospital, stroke, myocardial infarction, and severe acute kidney injury. The predictive model was constructed using the least absolute shrinkage and selection operator as well as multivariable logistic regression. The model was assessed in terms of the areas under receiver operating characteristic curves, calibration, and decision curve analysis. Results: The primary outcome occurred in 129 patients (2.1%) in the development cohort and 71 (5.8%) in the validation cohort. Six variables were retained in the predictive model: New York Heart Association class, diabetes, glucose, blood urea nitrogen, operation time, and red blood cell transfusion during surgery. The C-statistics were 0.735 (95% CI, 0.686-0.784) in the development cohort and 0.761 (95% CI, 0.694-0.828) in the validation cohort. For both cohorts, calibration plots showed good agreement between predicted and actual observations, and ecision curve analysis showed clinical usefulness. In contrast, the well-established SinoSCORE did not accurately predict the primary outcome in either cohort. Conclusions: This predictive nomogram based on six easily accessible variables may serve as an "early warning" system to identify patients at high risk of major complications after valve surgery. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT04476134].

miR-210 promotes hepatocellular carcinoma progression by modulating macrophage autophagy through PI3K/AKT/mTOR signaling.

BACKGROUND: Tumor-associated macrophages (TAMs) play an important role in tumor development. Increasing research suggests that miR-210 may promote the progression of tumor virulence, but whether its pro-carcinogenic effect in primary hepatocellular carcinoma (HCC) is via an action on M2 macrophages has not been examined. METHODS: Differentiation of THP-1 monocytes into M2-polarized macrophages was induced with phorbol myristate acetate (PMA) and IL-4, IL-13. M2 macrophages were transfected with miR-210 mimics or miR-210 inhibitors. Flow cytometry was used to identify macrophage-related markers and apoptosis levels. The autophagy level of M2 macrophages, expression of PI3K/AKT/mTOR signaling pathway-related mRNAs and protein were detected by qRT-PCR and Western blot. HepG2 and MHCC-97H HCC cell lines were cultured with M2 macrophages conditioned medium to explore the effects of M2 macrophage-derived miR-210 on the proliferation, migration, invasion and apoptosis of HCC cells. RESULTS: qRT-PCR showed increased expression of miR-210 in M2 macrophages. Autophagy-related gene and protein expression was enhanced in M2 macrophages transfected with miR-210 mimics, while apoptosis-related proteins were decreased. MDC staining and transmission electron microscopy observed the accumulation of MDC-labeled vesicles and autophagosomes in M2 macrophages in the miR-210 mimic group. The expression of PI3K/AKT/mTOR signaling pathway in M2 macrophages was reduced in miR-210 mimic group. HCC cells co-cultured with M2 macrophages transfected with miR-210 mimics exhibited enhanced proliferation and invasive ability as compared to the control group, while apoptosis levels were reduced. Moreover, promoting or inhibiting autophagy could enhance or abolish the above observed biological effects, respectively. CONCLUSIONS: miR-210 can promote autophagy of M2 macrophages via PI3K/AKT/mTOR signaling pathway. M2 macrophage-derived miR-210 promotes the malignant progression of HCC via autophagy, suggesting that macrophage autophagy may serve as a new therapeutic target for HCC, and targeting miR-210 may reset the effect of M2 macrophages on HCC.

One-Step, On-Site Chemical Printing of a 3D Plasmon-Coupled Silver Nanocoral Substrate toward SERS-Based POCT.

Surface-enhanced Raman scattering (SERS) with the advantages of high sensitivity, nondestructive analysis, and a unique fingerprint effect shows great potential in point-of-care testing (POCT). However, SERS faces challenges in rapidly constructing a substrate with high repeatability, homogeneity, and sensitivity, which are the key factors that restrict its practical applications. In this study, we propose a one-step chemical printing strategy for synthesizing a three-dimensional (3D) plasmon-coupled silver nanocoral (AgNC) substrate (only need about 5 min) without any pretreatments and complex instruments. The galvanic replacement between AgNO3 and Cu sheets will provide both Ag0 for the formation of silver nanostructures and Cu2+ for the polymerization of fish sperm DNA (FSDNA). The protection of AgNCs is facilitated by the crosslinked FSDNA, which can improve the stability of the substrate and promote the control of its coral-like morphology. The obtained substrate displays excellent capacity of signal enhancement due to the 3D plasmon coupling both between nanocoral tentacles and between nanocorals and Cu sheets as well. Therefore, the AgNC substrates display high activity (enhancement factor = 1.96 × 108) and uniformity (RSD < 6%). Food colorants have been widely used in various foods to improve their color, but the inevitable toxicity of colorants seriously threatens food safety. Therefore, the proposed AgNC substrates were used to directly quantify three kinds of weak-affinity food colorant molecules including Brilliant Blue, Allura Red, and Sunset Yellow assisted by the capture by cysteamine hydrochloride (CA), showing the detection limits (S/N = 3) of 0.053, 0.087, and 0.089 ppm, respectively. The SERS method has been further applied in the detection of the three kinds of food colorants in both complex food samples and urine with recoveries of 91-119%. The satisfactory detection results suggest that the facile preparation strategy of AgNC substrates will be widely used in SERS-based POCT to promote the development of food safety and on-site healthcare.

Preparation of the monoclonal antibody against Nile tilapia Igλ and study on the Igλ+ B cell subset in Nile tilapia.

Immunoglobulins (Igs) are important effector molecules that mediate humoral immunity. A typical Ig consists of two heavy and two light chains. In teleosts, three Ig heavy chain isotypes (Igµ, Igδ and Igτ) and three Ig light chain isotypes (Igκ, Igλ and Igσ) have been identified. Compared to the heavy chains, teleost Ig light chains have been poorly studied due to the lack of antibodies. In this study, a mouse anti-Nile tilapia Igλ monoclonal antibody (mAb) was prepared, which could specifically recognize Igλ in serum and Igλ+ B cells in tissues. Further, the composition of IgM+ and Igλ+ B cell subsets was analyzed using this antibody and a mouse anti-tilapia IgM heavy chain mAb. The ratio of IgM+Igλ+ B cells to total IgM+ B cells in head kidney and peripheral blood was about 30%, while that in spleen was about 50%; the ratio of IgM-Igλ+ B cells to total Igλ+ B cells in head kidney and peripheral blood was about 45%, while that in spleen was about 25%. The IgM-Igλ+ B cells was speculated to be IgT+ B cells. Finally, we detected an increase in the level of specific antibodies against the surface antigen-Sip of Streptococcus agalactiae in serum after S. agalactiae infection, indicating that mouse anti-tilapia Igλ mAb can be used to detect the antibody level after immunization of Nile tilapia, which lays a foundation for the evaluation of immunization effect of tilapia vaccine.

Large volume acute normovolemic hemodilution in patients undergoing cardiac surgery with intermediate-high risk of transfusion: A randomized controlled trial.

STUDY OBJECTIVE: To investigate whether large volume acute normovolemic hemodilution (L-ANH), compared with moderate acute normovolemic hemodilution (M-ANH), can reduce perioperative allogeneic blood transfusion in patients with intermediate-high risk of transfusion during cardiac surgery with cardiopulmonary bypass (CPB). DESIGN: Prospective randomized controlled trial. SETTING: University hospital. PATIENTS: Patients with transfusion risk understanding scoring tool ("TRUST") ≥2 points undergoing cardiac surgery with CPB in the Second Affiliated Hospital of Zhejiang University from May 2020 to January 2021 were included. INTERVENTIONS: The patients were randomly assigned with a 1:1 ratio to M-ANH (5 to 8 mL/kg) or L-ANH (12 to 15 mL/kg). MEASUREMENTS: The primary outcome was perioperative red blood cell (RBC) transfusion units. The composite outcome included new-onset atrial fibrillation, pulmonary infection, cardiac surgery associated acute kidney injury (CSA-AKI) class ≥2, surgical incision infection, postoperative excessive bleeding, and resternotomy. MAIN RESULTS: Total 159 patients were screened and 110 (55 L-ANH and 55 M-ANH) were included for final analysis. Removed blood volume of L-ANH is significantly higher than M-ANH (886 ± 152 vs. 395 ± 86 mL, P < 0.001). Perioperative RBC transfusion was median 0 unit ([25th, 75th] percentiles: 0-4.4) in M-ANH group vs. 0 unit ([25th, 75th] percentiles: 0-2.0) in L-ANH group (P = 0.012) and L-ANH was associated with lower incidence of transfusion (23.6% vs. 41.8%, P = 0.042, rate difference: 0.182, 95% confidence interval [0.007-0.343]). The incidence of postoperative excessive bleeding was significantly lower in L-ANH vs. M-ANH (3.6% vs. 18.2%, P = 0.029, rate difference: 0.146, 95% confidence interval [0.027-0.270]) without significant difference for other second outcomes. The volume of ANH was inversely related to perioperative RBC transfusion units (Spearman r = -0.483, 95% confidence interval [-0.708 to -0.168], P = 0.003), and L-ANH in cardiac surgery was associated with a significantly reduced risk of perioperative RBC transfusion (odds ratio: 0.43, 95% confidence interval: 0.19-0.98, P = 0.044). CONCLUSIONS: Compared with M-ANH, L-ANH during cardiac surgery inclined to be associated with reduced perioperative RBC transfusion and the volume of RBC transfusion was inversely proportional to the volume of ANH. In addition, LANH during cardiac surgery was associated with a lower incidence of postoperative excessive bleeding.